Ophthalmic Delivery

Targeted Agent for Eye Diseases

In preclinical studies, topical ophthalmic and systemic delivery of elamipretide have produced favorable effects in both retinal and corneal diseases. In addition, elamipretide may effectively address the mitochondria-associated defects in diseases such as diabetic macular edema, Fuchs Endothelial Corneal Dystrophy, genetic mitochondrial optic neuropathies (such as Leber’s Hereditary Optic Neuropathy) and age-related macular degeneration. 17 Patients suffering from each of these disorders have been studied in Stealth’s clinical trials.

Elamipretide (Ophthalmic Delivery)Studies suggest elamipretide appears to reach the inner membrane of damaged mitochondria by penetrating first the cell membrane and then the mitochondrial membrane. In preclinical and clinical studies, elamipretide has shown no effect on healthy mitochondrial or cellular function.6,39,42

Therapeutic Potential

Elamipretide has been studied in patients with diabetic macular edema.48 Elamipretide is being studied in retinal diseases including mitochondrial optic neuropathies such as Leber’s Hereditary Optic Neuropathy and dry age related macular degeneration.

Leber’s Hereditary Optic Neuropathy

Data suggest that elamipretide has potential for treating Leber’s Hereditary Optic Neuropathy (LHON), an inherited mitochondrial disease that results in sudden and profound loss of vision in both eyes of patients, typically beginning before age 40. Each year 100 people in the U.S. suffer from central vision loss due to LHON and approximately 35,000 people worldwide have been diagnosed with LHON.28,33

Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is a common eye condition and a leading cause of vision loss among people over the age of 50. AMD causes damage to the macula, the part of the eye needed for sharp, central vision. This is the most sensitive part of the retina, which is located in the back of the eye. AMD is characterized by the presence of deposits of acellular debris between the retinal pigment epithelium and Bruch’s membrane, which are called drusen. People with AMD experience distorted or blurred vision, and they may have difficulty performing activities under low light, such as driving or reading at night. As AMD progresses, a blurred area commonly develops near the center of vision. Over time, the area may grow larger or blank spots may develop.16,17

Fuchs’ Corneal Endothelial Dystrophy

Fuchs’ is a late-onset, progressive disease of the cornea characterized by a reduction of endothelial cells, and can lead to edema or even blindness in more advanced cases. Elamipretide targets the inner mitochondrial membrane to help preserve mitochondrial energetics, loss of which is thought to lead to the onset of Fuchs’.

Elamipretide in Clinical Trials

For more information about clinical trials, visit www.clinicaltrials.gov and search “Stealth BioTherapeutics.”

Diseases and Disorders Associated with Mitochondria

Mitochondrial disorders are believed to arise either as a result of inherited genetic defects or through damage caused by a variety of common diseases. 37